Synthesis of betulinic acid derivatives with activity against human melanoma.


:Betulinic acid has been modified at C-3, C-20, and C-28 positions and the toxicity of the derivatives has been evaluated against cultured human melanoma (MEL-2) and human epidermoid carcinoma of the mouth (KB) cell lines. This preliminary investigation demonstrates that simple modifications of the parent structure of betulinic acid can produce potentially important derivatives, which may be developed as antitumor drugs.


Bioorg Med Chem Lett


Kim DS,Pezzuto JM,Pisha E




Has Abstract


1998-07-07 00:00:00














  • Evaluation of a series of bicyclic CXCR2 antagonists.

    abstract::The CXCR2 SAR of a series of bicyclic antagonists such as the 2-aminothiazolo[4,5-d]pyrimidine 3b was investigated by systematic variation of the fused pyrimidine-based heterocyclic cores. Replacement of the aminothiazole ring with a 2-thiazolone alternative led to a series of thiazolo[4,5-d]pyrimidine-2(3H)-one antag...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Walters I,Austin C,Austin R,Bonnert R,Cage P,Christie M,Ebden M,Gardiner S,Grahames C,Hill S,Hunt F,Jewell R,Lewis S,Martin I,David Nicholls,David Robinson

    更新日期:2008-01-15 00:00:00

  • Synthesis and bioactivity of 3,5-dimethylpyrazole derivatives as potential PDE4 inhibitors.

    abstract::A series of 3,5-dimethylpyrazole derivatives containing 5-phenyl-2-furan moiety were designed and synthesized as phosphodiesterase type 4 (PDE4) inhibitors. Bioassay results showed that the title compounds exhibited considerable inhibitory activity against PDE4B and blockade of LPS-induced TNFα release. Among the desi...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Hu DK,Zhao DS,He M,Jin HW,Tang YM,Zhang LH,Song GP,Cui ZN

    更新日期:2018-10-15 00:00:00

  • Convenient method for the addition of disulfides to alkenes.

    abstract::Catalytic disulfenylation reaction of alkenes by common Lewis acids has been investigated in detail. While reactions by FeCl(3) were feasible with cycloalkenes and other simple alkenes, much faster and excellent conversions were possible by AlCl(3) even with the substrates less reactive toward FeCl(3). ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Yamagiwa N,Suto Y,Torisawa Y

    更新日期:2007-11-15 00:00:00

  • Discovery of a novel olefin derivative as a highly potent and selective acetyl-CoA carboxylase 2 inhibitor with in vivo efficacy.

    abstract::Novel acetyl-CoA carboxylase 2 (ACC2) selective inhibitors were identified by the conversion of the alkyne unit of A-908292 to the olefin linker. Modification of the center and left part of the lead compound 1b improved the ACC2 inhibitory activity and CYP450 inhibition profile, and afforded a highly selective ACC2 in...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Nishiura Y,Matsumura A,Kobayashi N,Shimazaki A,Sakamoto S,Kitade N,Tonomura Y,Ino A,Okuno T

    更新日期:2018-08-01 00:00:00

  • Design, synthesis, and antibacterial activity of 2,5-dihydropyrrole formyl hydroxyamino derivatives as novel peptide deformylase inhibitors.

    abstract::The synthesis and antibacterial activity of 2,5-dihydropyrrole formyl hydroxyamino derivatives are reported. The antibacterial activities of these derivatives were evaluated, and some of these derivatives showed better in vitro antibacterial activity than existing drugs, including penicillin, ciprofloxacin, vancomycin...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Shi W,Duan Y,Qian Y,Li M,Yang L,Hu W

    更新日期:2010-06-15 00:00:00

  • Isoindol-1,3-dione and isoindol-1-one derivatives with high binding affinity to beta-amyloid fibrils.

    abstract::Based on the structural features of Indoprofen and PIB, a series of isoindol-1,3-diones 1a-k and isoindol-1-ones 2a-l were designed and synthesized. These 23 compounds were evaluated by competitive binding assay against aggregated Abeta42 fibrils using [(125)I]TZDM. All the isoindolone derivatives showed very good bin...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Lee HJ,Lim SJ,Oh SJ,Moon DH,Kim DJ,Tae J,Yoo KH

    更新日期:2008-03-01 00:00:00

  • Design, synthesis and biological evaluation of novel potent MDM2/p53 small-molecule inhibitors.

    abstract::Regioselective synthesis, biological evaluation and 3D-molecular modeling for a series of novel diastereomeric 2-thioxo-5H-dispiro[imidazolidine-4,3-pyrrolidine-2,3-indole]-2,5(1H)-diones are described. The studied compounds have been tentatively identified as potent small molecule MDM2/p53 PPI inhibitors and can ther...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Ivanenkov YA,Vasilevski SV,Beloglazkina EK,Kukushkin ME,Machulkin AE,Veselov MS,Chufarova NV,Chernyaginab ES,Vanzcool AS,Zyk NV,Skvortsov DA,Khutornenko AA,Rusanov AL,Tonevitsky AG,Dontsova OA,Majouga AG

    更新日期:2015-01-15 00:00:00

  • Design and synthesis of conformationally constrained 3-(N-alkylamino)propylphosphonic acids as potent agonists of sphingosine-1-phosphate (S1P) receptors.

    abstract::A series of conformationally constrained 3-(N-alkylamino)propylphosphonic acids were systematically synthesized and their activities as S1P receptor agonists were evaluated. Several pyrrolidine and cyclohexane analogs had S1P receptor profiles comparable to the acyclic lead compound, 3-(N-tetradecylamino)propylphospho...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Yan L,Hale JJ,Lynch CL,Budhu R,Gentry A,Mills SG,Hajdu R,Keohane CA,Rosenbach MJ,Milligan JA,Shei GJ,Chrebet G,Bergstrom J,Card D,Rosen H,Mandala SM

    更新日期:2004-10-04 00:00:00

  • New polyphenols active on beta-amyloid aggregation.

    abstract::New polyphenol classes have been tested against amyloid-beta peptide aggregation. We have identified four novel polyphenols which could be efficient fibril inhibitors in Alzheimer's disease: malvidin and its glucoside and curculigosides B and D. We suggest that molecules with the particular C(6)-linkers-C(6) structure...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Rivière C,Richard T,Vitrac X,Mérillon JM,Valls J,Monti JP

    更新日期:2008-01-15 00:00:00

  • A hit to lead discovery of novel N-methylated imidazolo-, pyrrolo-, and pyrazolo-pyrimidines as potent and selective mTOR inhibitors.

    abstract::A series of N-7-methyl-imidazolopyrimidine inhibitors of the mTOR kinase have been designed and prepared, based on the hypothesis that the N-7-methyl substituent on imidazolopyrimidine would impart selectivity for mTOR over the related PI3Kα and δ kinases. The corresponding N-Me substituted pyrrolo[3,2-d]pyrimidines a...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Lee W,Ortwine DF,Bergeron P,Lau K,Lin L,Malek S,Nonomiya J,Pei Z,Robarge KD,Schmidt S,Sideris S,Lyssikatos JP

    更新日期:2013-09-15 00:00:00

  • Synthesis and evaluation of a novel series of indoloisoquinolines as small molecule anti-malarial leads.

    abstract::A group of novel synthetic indoloisoquinolines was prepared and its potential as a novel series of small-molecule anti-malarial leads was assessed. The structure-activity relationship on variation of three distinct regions of chemical space was investigated. A lead compound was generated with an activity close to that...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Horrocks P,Fallon S,Denman L,Devine O,Duffy LJ,Harper A,Meredith EL,Hasenkamp S,Sidaway A,Monnery D,Phillips TR,Allin SM

    更新日期:2012-02-15 00:00:00

  • New triple-helix DNA stabilizing agents.

    abstract::Several substituted quinolin-4-amines and heteroaromatic analogs were synthesized and evaluated for interaction with triplex polydA.2polydT and duplex polydA.polydT by using UV-thermal melting experiments. Excellent triple-helix DNA ligands with high affinity toward T.A.T triplets and triple/duplex selectivity were de...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Strekowski L,Hojjat M,Wolinska E,Parker AN,Paliakov E,Gorecki T,Tanious FA,Wilson WD

    更新日期:2005-02-15 00:00:00

  • Synthesis of new bergenin derivatives as potent inhibitors of inflammatory mediators NO and TNF-α.

    abstract::Bergenin is an isocoumarin natural product which aides in fat loss, healthy weight maintenance, enhancing the lipolytic effects of norepinephrine, inhibiting the formation of interleukin 1α and cyclooxygenases-2. Here we describe the anti-inflammatory activity of new bergenin derivatives 1-15 in the respiratory burst ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Shah MR,Arfan M,Amin H,Hussain Z,Qadir MI,Choudhary MI,VanDerveer D,Mesaik MA,Soomro S,Jabeen A,Khan IU

    更新日期:2012-04-15 00:00:00

  • Design and synthesis of tamoxifen derivatives as a selective estrogen receptor down-regulator.

    abstract::We designed and synthesized an estrogen receptor (ER) down-regulator (5), which is a derivative of tamoxifen with a long alkyl side chain. Compound 5 effectively reduced ER protein levels in MCF-7 cells and had an antagonistic effect. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Shoda T,Okuhira K,Kato M,Demizu Y,Inoue H,Naito M,Kurihara M

    更新日期:2014-01-01 00:00:00

  • Synthesis and evaluation of GGPP geometric isomers: divergent substrate specificities of FTase and GGTase I.

    abstract::A stereocontrolled synthetic route has been used to prepare two of the geometric isomers of all-trans-GGPP. Neither of these isomers is effective substrates for mammalian GGTase I, but 3 is a potent inhibitor of this enzyme (IC(50)=100 nM). Surprisingly, both compounds are effective substrates for mammalian FTase. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Zahn TJ,Whitney J,Weinbaum C,Gibbs RA

    更新日期:2001-06-18 00:00:00

  • Structural factors contributing to the Abl/Lyn dual inhibitory activity of 3-substituted benzamide derivatives.

    abstract::To investigate why 3-substituted benzamide derivatives show dual inhibition of Abl and Lyn protein tyrosine kinases, we determined their inhibitory activities against Abl and Lyn, carried out molecular modeling, and conducted a structure-activity relationship study with the aid of a newly determined X-ray structure of...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Horio T,Hamasaki T,Inoue T,Wakayama T,Itou S,Naito H,Asaki T,Hayase H,Niwa T

    更新日期:2007-05-15 00:00:00

  • Synthesis of β-boswellic acid derivatives as cytotoxic and apoptotic agents.

    abstract::A series of β-boswellic acid derivatives were synthesized and evaluated for anticancer activity. One of the lead analog 4f displayed significant anticancer activity against a panel of cancer cells as well as substantially inhibited colony formation in HCT-116 cells. Furthermore, 4f was found to be a potent inducer of ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Kumar A,Qayum A,Sharma PR,Singh SK,Shah BA

    更新日期:2016-01-01 00:00:00

  • 2-(Anilino)imidazolines and 2-(benzyl)imidazoline derivatives as h5-HT1D serotonin receptor ligands.

    abstract::2-(Anilino)imidazolines were identified as novel human 5-HT(1D) receptor ligands, but offered no particular advantage over previously reported 2-(benzyl)imidazolines. Pharmacokinetic and functional data were obtained for selected 2-(benzyl)imidazoline derivatives. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Prisinzano T,Dukat M,Law H,Slassi A,MacLean N,DeLannoy I,Glennon RA

    更新日期:2004-09-20 00:00:00

  • A hypoxia-activated antibacterial prodrug.

    abstract::A prodrug based on a known antibacterial compound is reported to target Staphylococcus aureus and Escherichia coli under reductive conditions. The prodrug was prepared by masking the N-terminus and side chain amines of a component lysine residue as 4-nitrobenzyl carbamates. Activation to liberate the antibacterial was...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Yeoh YQ,Horsley JR,Polyak SW,Abell AD

    更新日期:2020-06-01 00:00:00

  • Highly potent and long-acting trimeric and tetrameric inhibitors of influenza virus neuraminidase.

    abstract::A set of trimeric and tetrameric derivatives 6-11 of the influenza virus neuraminidase inhibitor zanamivir 1 have been synthesized by coupling a common monomeric zanamivir derivative 3 onto various multimeric carboxylic acid core groups. These discrete multimeric compounds are all significantly more antiviral than zan...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Watson KG,Cameron R,Fenton RJ,Gower D,Hamilton S,Jin B,Krippner GY,Luttick A,McConnell D,MacDonald SJ,Mason AM,Nguyen V,Tucker SP,Wu WY

    更新日期:2004-03-22 00:00:00

  • New antiprotozoal agents: their synthesis and biological evaluations.

    abstract::Here we report identification of new lead compounds based on quinoline and indenoquinolines with variable side chains as antiprotozoal agents. Quinolines 32, 36 and 37 (Table 1) and indenoquinoline derivatives 14 and 23 (Table 2) inhibit the in vitro growth of the Trypanosoma cruzi, Trypanosoma brucei, Trypanosoma bru...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Upadhayaya RS,Dixit SS,Földesi A,Chattopadhyaya J

    更新日期:2013-05-01 00:00:00

  • Novel PARP-1 inhibitors based on a 2-propanoyl-3H-quinazolin-4-one scaffold.

    abstract::Poly(ADP-ribose)polymerase-I (PARP-1) enzyme is involved in maintaining DNA integrity and programmed cell death. A virtual screening of commercial libraries led to the identification of five novel scaffolds with inhibitory profile in the low nanomolar range. A hit-to-lead optimization led to the identification of a gr...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Giannini G,Battistuzzi G,Vesci L,Milazzo FM,De Paolis F,Barbarino M,Guglielmi MB,Carollo V,Gallo G,Artali R,Dallavalle S

    更新日期:2014-01-15 00:00:00

  • Synthesis of hybrid acetogenins, alpha,beta-unsaturated-gamma-lactone-free nitrogen-containing heterocyclic analogues, and their cytotoxicity against human cancer cell lines.

    abstract::A series of alpha,beta-unsaturated-gamma-lactone-free nitrogen-containing heterocyclic analogues of solamin, a natural mono-THF acetogenin, have been synthesized and their cytotoxicity was investigated against 39 tumor cell lines. One of them, 1-methylpyrazol-5-yl derivative, showed selective increase of cytotoxicity ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Kojima N,Fushimi T,Maezaki N,Tanaka T,Yamori T

    更新日期:2008-03-01 00:00:00

  • Anti-inflammatory property of the urinary metabolites of nobiletin in mouse.

    abstract::Nobiletin, a major component of polymethoxyflavones in citrus fruits, has a broad spectrum of health beneficial properties including anti-inflammatory and anti-carcinogenic activities. The metabolite identification of nobiletin in mouse urine has concluded that it undergoes mono-demethylation (3'- and 4'-demethylnobil...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Li S,Sang S,Pan MH,Lai CS,Lo CY,Yang CS,Ho CT

    更新日期:2007-09-15 00:00:00

  • Glycan multivalency effects toward albumin enable N-glycan-dependent tumor targeting.

    abstract::Multivalent interactions play an essential role in molecular recognition in living systems. These effects were employed to target tumor cells using albumin clusters bearing ∼10 molecules of asparagine-linked glycans (N-glycans). Noninvasive near-infrared fluorescence imaging clearly revealed A431 tumors implanted in B...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Ogura A,Tahara T,Nozaki S,Onoe H,Kurbangalieva A,Watanabe Y,Tanaka K

    更新日期:2016-05-01 00:00:00

  • Discovery of piperidine ethers as selective orexin receptor antagonists (SORAs) inspired by filorexant.

    abstract::Highly selective orexin receptor antagonists (SORAs) of the orexin 2 receptor (OX2R) have become attractive targets both as potential therapeutics for insomnia as well as biological tools to help further elucidate the underlying pharmacology of the orexin signaling pathway. Herein, we describe the discovery of a novel...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Raheem IT,Breslin MJ,Bruno J,Cabalu TD,Cooke A,Cox CD,Cui D,Garson S,Gotter AL,Fox SV,Harrell CM,Kuduk SD,Lemaire W,Prueksaritanont T,Renger JJ,Stump C,Tannenbaum PL,Williams PD,Winrow CJ,Coleman PJ

    更新日期:2015-02-01 00:00:00

  • Asymmetric synthesis of novel alpha-amino acids with beta-branched side chains.

    abstract::An asymmetric synthesis of alpha-amino acids with novel beta-branched side chains has been implemented. The syntheses feature a p-toluenesulfinylimine induced chiral Strecker approach and were found to be applicable to the introduction of both aliphatic and aromatic beta-branched sidechains for preparation of previous...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Zhang M,Porte A,Diamantidis G,Sogi K,Kubrak D,Resnick L,Mayer SC,Wang Z,Kreft AF,Harrison BL

    更新日期:2007-05-01 00:00:00

  • Synthesis and biological characterization of a series of novel diaryl amide M₁ antagonists.

    abstract::Utilizing a combination of high-throughput and multi-step synthesis, SAR in a novel series of M(1) acetylcholine receptor antagonists was rapidly established. The efforts led to the discovery the highly potent M(1) antagonists 6 (VU0431263), and 8f (VU0433670). Functional Schild analysis and radioligand displacement e...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Poslusney MS,Sevel C,Utley TJ,Bridges TM,Morrison RD,Kett NR,Sheffler DJ,Niswender CM,Daniels JS,Conn PJ,Lindsley CW,Wood MR

    更新日期:2012-11-15 00:00:00

  • Synthesis of 2'-O,4'-C-alkylene-bridged ribonucleosides and their evaluation as inhibitors of HCV NS5B polymerase.

    abstract::The synthesis of 2'-O,4'-C-methylene-bridged bicyclic guanine ribonucleosides bearing 2'-C-methyl or 5'-C-methyl modifications is described. Key to the successful installation of the methyl functionality in both cases was the use of a one-pot oxidation-Grignard procedure to avoid formation of the respective unreactive...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Chapron C,Glen R,La Colla M,Mayes BA,McCarville JF,Moore S,Moussa A,Sarkar R,Seifer M,Serra I,Stewart A

    更新日期:2014-06-15 00:00:00

  • Toxocara canis: Larvicidal activity of fatty acid amides.

    abstract::Considering the therapeutic potential of fatty acid amides, the present study aimed to evaluate their in vitro activity against Toxocara canis larvae and their cytotoxicity for the first time. Linoleylpyrrolidilamide was the most potent, with a minimal larvicidal concentration (MLC) of 0.05 mg/mL and 27% cytotoxicity ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Mata-Santos T,D'Oca CDRM,Mata-Santos HA,Fenalti J,Pinto N,Coelho T,Berne ME,da Silva PEA,D'Oca MGM,Scaini CJ

    更新日期:2016-02-01 00:00:00